Galectin-3 Functions as an Adhesion Molecule to Support Eosinophil Rolling and Adhesion under Conditions of Flow

Abstract

Allergic inflammation involves the mobilization and trafficking of eosinophils to sites of inflammation. Galectin-3 (Gal-3) has been shown to play a critical role in eosinophil recruitment and airway allergic inflammation in vivo. The role played by Gal-3 in human eosinophil trafficking was investigated. Eosinophils from allergic donors expressed elevated levels of Gal-3 and demonstrated significantly increased rolling and firm adhesion on immobilized VCAM-1 and, more surprisingly, on Gal-3 under conditions of flow. Inhibition studies with specific mAbs as well as lactose demonstrated that: 1) eosinophil-expressed Gal-3 mediates rolling and adhesion on VCAM-1; 2) α4 integrin mediates eosinophil rolling on immobilized Gal-3; and 3) eosinophil-expressed Gal-3 interacts with immobilized Gal-3 through the carbohydrate recognition domain of Gal-3 during eosinophil trafficking. These findings were further confirmed using inflamed endothelial cells. Interestingly, Gal-3 was found to bind to α4 integrin by ELISA, and the two molecules exhibited colocalized expression on the cell surface of eosinophils from allergic donors. These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.

Role of Galectin-3 in Leukocyte Recruitment in a Murine Model of Lung Infection by Streptococcus pneumoniae

“…Previous in vitro studies have demonstrated that galectin-3 mediates the adhesion of neutrophils to the endothelium by directly cross-linking them (29,47), raising the possibility that galectin-3, in agreement with our present data, initiates neutrophil adhesion to the endothelium during streptococcal pneumonia. Indeed, such a function for galectin-3 as an adhesion molecule has been recently suggested for eosinophils and breast carcinoma cells (70,71). Furthermore, the group of Hughes has demonstrated that galectin-3 enhances the migration of breast carcinoma cells through a three-dimensional matrix (72).…”

“…Furthermore, the group of Hughes has demonstrated that galectin-3 enhances the migration of breast carcinoma cells through a three-dimensional matrix (72). Notably, Rao et al recently demonstrated that galectin-3 is presented on the surface of IL-1␣-stimulated endothelial cells (71). In addition, our previous microscope observations suggest that the occurrence of extracellular galectin-3 oligomerization appears to be concentrated at the interface of endothelium and adherent neutrophils, especially those localized at tricellular corners, where the borders of three endothelial cells intersect (47).…”

Eosinophils and Trichinella infection: toxic for the parasite and the host?

“…Galectin-3 (Gal-3) has a crucial role in eosinophil recruitment and airway allergic inflammation of mice [21]. In humans, eosinophils from allergic donors express elevated levels of Gal-3, which co-localizes with α integrin and increase the rolling and firm adhesion of eosinophils on the VCAM-1 of endothelial cells [22].…”

Galectins: Structures, Binding Properties and Function in Cell Adhesion

“…Galectin-3 mediated angiogenesis depends on the growth factors VEGF and bFGF (Markowska et al, 2010). Another interesting function of galectin-3 is the chemotattraction of monocytes via a G-protein coupled receptor pathway and the role in eosinophil rolling to sites of inflammation (Rao et al, 2007;Sano et al, 2000). Most of those functions can only be performed by full length galectin-3 showing the importance of glycan binding and oligomerisation of the protein (Markowska et al, 2010;Sano et al, 2000).…”